Development of Spectral X-Ray Phase-Contrast Micro-CT Project Summary A challenging aspect of in vivo micro-CT relates to the required deleterious radiation dose levels - particularly for studies required to follow the same subject longitudinally. The main constraint is the poor attenuation contrast for x-rays in soft tissue and the need for long imaging times. Researchers have studied the use of multi-energy (or spectral) x-ray acquisitions to perform material decomposition with micro-CT systems, but the versatility of these methods is again constrained by the same contrast-dose trade-off. Phase-contrast imaging (PCI) can provide significant phase-enhanced contrast at higher energies, thus potentially reducing micro-CT dose. However, existing PCI methods still require high dose and long imaging times for accurate phase retrieval. We have recently developed an algorithmic approach to spectral PCI that enables dose and imaging times commensurate with attenuation imaging. Our hypothesis is that PCI performed under normal clinical constraints can yield better tissue quantitation and small feature delineation at lower dose than attenuation imaging. We shall develop a unique spectral micro-CT system with both PCI and non-PCI capabilities to test this hypothesis. A key system component will be an innovative high-performance, high-resolution photon- counting detector (PCD) to be developed jointly under this grant by the University of Houston and Advacam s.r.o. Two non-interferometric PCI geometries will be evaluated. The first specific aim is to design the micro- CT system based on considerations such as source kVp and the PCD sensor thickness, pixel size, and energy bin configuration. PCI-specific criteria include magnification and the x-ray mask properties. Optimization studies will be carried out for both the PCI and the non-PCI modes. For Aim 2, we will work with Advacam to develop the wide-area, high frame rate and high Z sensor PCD for the system. The high-performance PCD will be constructed based on Medipix3RX ASIC technology and will feature high resolution and built-in spectral correction schemes and fast readouts. Under Aim 3, the micro-CT unit will be constructed and energy calibration and correction schemes will be developed to allow efficient system performance. Our fourth specific aim is to compare the performance of the PCI and non-PCI modes of spectral micro-CT with physical phantoms and animal studies to evaluate the enhancement of low contrast sensitivity. In vivo studies using liposomal iodine nanoparticles will examine the ability of PCI to distinguish differences in blood vascularity for treatment- responsive and treatment-resistive prostate cancer models in mice.